Ambident Nucleophilic Substitution: Understanding Non-HSAB Behavior through Activation Strain and Conceptual DFT Analyses |
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| Authors: | Tom Bettens Dr Mercedes Alonso Prof Dr Frank De Proft Dr Trevor A Hamlin Prof Dr F Matthias Bickelhaupt |
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| Institution: | 1. Eenheid Algemene Chemie (ALGC), Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium;2. Department of Theoretical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Amsterdam Center for Multiscale Modeling (ACMM), Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands |
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| Abstract: | The ability to understand and predict ambident reactivity is key to the rational design of organic syntheses. An approach to understand trends in ambident reactivity is the hard and soft acids and bases (HSAB) principle. The recent controversy over the general validity of this principle prompted us to investigate the competing gas-phase SN2 reaction channels of archetypal ambident nucleophiles CN−, OCN−, and SCN− with CH3Cl (SN2@C) and SiH3Cl (SN2@Si), using DFT calculations. Our combined analyses highlight the inability of the HSAB principle to correctly predict the reactivity trends of these simple, model reactions. Instead, we have successfully traced reactivity trends to the canonical orbital-interaction mechanism and the resulting nucleophile–substrate interaction energy. The HOMO–LUMO orbital interactions set the trend in both SN2@C and SN2@Si reactions. We provide simple rules for predicting the ambident reactivity of nucleophiles based on our Kohn–Sham molecular orbital analysis. |
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| Keywords: | activation strain model ambident reactivity conceptual density functional theory density functional calculations nucleophilic substitution reactions |
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